1. Emerging Programs of DES with Biodegradable Polymers
Biodegradable Polymer DES Programs
Emerging Programs of DES with Biodegradable Polymers
Ricardo A. Costa, MD, PhD
Institute Dante Pazzanese, Sao Paulo, Brazil
Monday, Feb. 20th 2017 – 11:24 to 11:32 am (8 minutes)
Empire Ballroom – The Omni Shoreham Hotel
Washington, DC, USA

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Grant/Research Support
Consulting Fees/Honoraria
Major Stock Shareholder/Equity
Royalty Income
Ownership/Founder
Intellectual Property Rights
Other Financial Benefit
Company Names

3. Conflict of Interest Statement
Ricardo A. Costa, MD, PhD
Research grant/consulting fees from Meril Life Sciences

4. Potential Advantages
Avoid problems related to temporary or permanent polymeric residue (late/very late recurrences, ST)
Optimize vascular healing
Maintain stent surface integrity (as opposed to webbing/delamination seen with durable polymers)
Shorten DAPT post-implant; thus, avoid bleeding complications without compromising safety
Maintain efficacy at inhibiting NIH

5. Emerging DES with BP Abluminus (Envision Scientific, India)
Alex (Balton, Poland)
BioMime (Meril Life Sciences, India)
FireHawk (MicroPort, China)
Inspiron (Scitech, Brazil)
BuMA (SinoMed, China)

6. Emerging DES with BP
Abluminus (Envision Scientific, India)

7. Antiproliferative agent: sirolimus
Combination of DES and BEB
Biodegradable polymer matrix
Completed released by 180 days
45” inflation time to ensure complete drug delivery

8. en-ABL 1 Clinical Trial - QCA Results*
Variable (40 pts/56 lesions)
Baseline
Final
6-Month
Lesion length, mm
19.8±14.2 -
Reference diameter, mm
2.46±0.45
2.61±0.43
2.53±0.43
MLD, mm
0.71±0.39
2.40±0.40
2.17±0.54
%DS
71.8±14.6
6.9±6.7
14.1±14.4
Late lumen loss, mm
0.24±0.30
*Cardiovascular Research Center, São Paulo, Brazil

9. Sammer TCT 2016

10. Sammer TCT 2016

11. Sammer TCT 2016

12. Sammer TCT 2016

13. Sammer TCT 2016

14. Emerging DES with BP Abluminus (Envision Scientific, India)
Alex (Balton, Poland)

15. Alex Sirolimus-Eluting Stent
Cobalt-chromium platform – 70 µm (Alex Plus – new design)
Bioabsorbable polymer coating – 5 µm (PLGA, absorbed in ~8 weeks)
Wide range of sizes ( mm diameter; 8-40 mm length)

16. Dariusz TCT 2016

17. Dariusz TCT 2016

20. Dariusz TCT 2016

21. Dariusz TCT 2016

22. PI: Dariusz Dudek (Krakow, Poland)

23. Emerging DES with BP Abluminus (Envision Scientific, India)
Alex (Balton, Poland)
BioMime (Meril Life Sciences, India)

27. *Cardiovascular Research Center, São Paulo, Brazil

32. BioMime Morph Registry – Kuala Lampur
222 patients with diffused CAD treated with Morph during Apr 2015 – September 2016
Baseline Characteristics
N = 222 (%)
Age, ≤ 60 Years
144 (64.9%)
Age, > 60 Years
78 (35.1%)
Diabetes Mellitus (DM)
56 (25.2%)
Hypertension(HTN)
48 (21.5%)
DM + HTN
104 (46.7%)

33. Procedural Information
Variable
N = 222 (%)
Vessel Treated with BioMime Morph
LAD
127 (57%)
LCx
10 (5%)
RCA
84 (38%)
Sizes
N = 222 (%)
Diameters of BioMime Morph
3.50 – 3.00 mm
68 (30.0%)
3.00 – 2.50 mm
135 (60.8%)
2.75 – 2.25 mm
19 (9.2%)
Lengths of BioMime Morph
30 mm
19 (8.0%)
40 mm
105 (47.5%)
50 mm
34 (15.5%)
60 mm
64 (29.0%)
Dilatation
N = 222, n (%)
Pre-Procedure
219 (98.7%)
Post-Procedure
222 (100.0%)
Antiplatelet Drugs
N = 222, n (%)
Aspirin + Clopidogrel
20 (54%)
Aspirin + Ticagrelor
17 (46%)

34. 6 Months follow-up data 1 & 6 months clinical follow-up data
At Procedure
(N = 222)
1 month f/up
6 month f/up
(N = 215)
Death
No Complications
222 (100 %)
100 (100 %)
215 (96.8 %)
Stent Thrombosis
Bleeding

35. Emerging DES with BP Abluminus (Envision Scientific, India)
Alex (Balton, Poland)
BioMime (Meril Life Sciences, India)
FireHawk (MicroPort, China)

36. Key Components Co-Cr stent with abluminal grooves
D,L-PLA absorbed after 9 mo and recover to metallic surface
Printing technology
Sirolimus
1/3 of
drug
dose of
Cypher

37. Stent Design - Isolated Abluminal Grooves
One of the main components of Target Eluting Technology.
Only in the straight parts of the strut.
The grooves designed on the outer surface of the stent allows targeting release of the drug to coronary vessel wall.
The depth of groove is about 1/3 of the strut, and the thickness of coating stored in the groove is about 10 microns ( ”)

38. TARGET Clinical Program
FIM
Enrollment
n=21
TARGET I Trial Enrollment
n=510
TARGET II Registry Enrollment
n=730
Workhorse Stent * Randomized Trial
n=460
Long FIREHAWK
(33 and 38mm) Registry, n=50
4mo Angio (95%) and OCT (70%) F/U
XIENCE V
n=230
FIREHAWK
n=230
9mo Angio F/U
(>=80%)
9mo Angio F/U
(>=80%)
1-Year Clinical F/U (>=95%) and Annually up to 5 Years (n=1,010)
Primary Clinical Endpoint: Device Oriented Composite of Cardiac Death, TVMI, or iTLR (Target Lesion Failure, TLF) at 1-Year (Objective Performance Criteria)

40. Early healing proved by 4m OCT from Target FIM study
Analyzed: 14 Stented Segments Every 0.3mm (1084 Cross-Sections), Struts
2.2%
1.6%
Optical Coherence Tomography, OCT
11108, 96.2%
0.1%

42. TARGET All Comers – Clinical Trial Design
Open label, non-inferiority trial
All patients with symptomatic CAD eligible for DES implantation
(no lesion/vessel limitations)
1,656 patients, 20 sites (Europe)
Subsets: QCA 176 pts; OCT 50 pts
100% monitoring
Firehawk Stent
n = 828
Xience EES
n = 828
Clinical/TLF
30d
6mo
12mo
13mo
2yr
3yr
4yr
5yr
Angio/OCT
50 Pts OCT Subset
176 Pts QCA Subset
Primary Endpoint: TLF (ARC defined) = Cardiac Death, Target Vessel MI, 12mo
Secondary Endpoint (powered): in-stent late 13mo; uncovered stent strut 3mo
Secondary Endpoints: 30d, 6mo, yr; Composite (all death, all MI, any revasc) at
each FU time point; QCA 13 mo; OCT 3 mo
Drug Therapy: ASA and thienopyridine > 6 months (per guidelines)

43. Emerging DES with BP Abluminus (Envision Scientific, India)
Alex (Balton, Poland)
BioMime (Meril Life Sciences, India)
FireHawk (MicroPort, China)
Inspiron (Scitech, Brazil)

44. Inspiron SES Thin-Strut Plataform CoCr – L605 Abluminal Coating
Biodegradable Polymer
Low Drug
Sirolimus
Cronus Plus™
75 μm strut thickness
PLA + PLGA
Abluminal only
5 μm layer thickness
Complete degradation in 6-9 months
Low dose
Inspiron™ 3.5 x 13 mm
Cypher™
3.5 x 13 mm
56 μg
129 μg

45. 6-month angiographic and IVUS outcomes
INSPIRON I Trial
6-month angiographic and IVUS outcomes
EuroIntervention 2014;9:
In-Stent late loss*
IVUS % NIH Obstruction
P < 0.001
P <0.001
26.5 ± 11.4
0.84 ± 0.45
7.8 ± 7.1
0.22 ± 0.17
*Primary EP
*Cardiovascular Research Center
São Paulo, Brazil

46. DESTINY Trial Study Design (Multicenter in 10 Brazilian Institutions)
170 patients (194 lesions)
Up to 2 de novo lesions
Vessels 2.5 – 3.5 mm
Single stent per lesion (up to 29 mm)
Primary EP
IS LL at 9 months
Non-inferiority
Randomization 2:1
Inspiron
(n=110 pts)
Biomatrix
(n=55 pts)
IVUS substudy*
(n=60 pts / 66 lesions)
9-month angiographic follow-up*
(164 pts [96.5%] / 187 lesions [96.4])
OCTsubstudy*
(n=21 pts / 25 leions)
*Cardiovascular Research Center, São Paulo, Brazil

47. DESTINY Trial 9-month QCA (in-stent).
Inspiron
Biomatrix P N
127 60
MLD, mm
2.44 ± 0.44
2.55 ± 0.40
0.09
DS, %
11.2 ± 11.3
9.7 ± 6.6
0.26
Late loss, mm*
0.20 ± 0.27
0.15 ± 0.20
<0.001 (NI)
Binary restenosis
3.2% (4)
1.7% (1)
0.56
*Study primary endpoint

48. DESTINY Trial OCT Safety endpoints
Total of 8,944 struts analyzed [SES: 5,801; BES: 3,143]
P = 0.021
P = 0.198
2.38 ± 2.20
0.51 ± 1.00
0.28 ± 1.06
0.53 ± 0.81
Uncovered Struts
Malapposed Struts

49. INSPIRON (N= 111 Patients) BIOMATRIX FLEX (N= 55 Patients)
DESTINY Trial Clinical events (up to 270 days)
INSPIRON (N= 111 Patients)
BIOMATRIX FLEX (N= 55 Patients)
P-value
MACCE
7/111 (6.30)
4/55 (7.30)
0.672
MACE
Death
0/111 (0.00)
0/55 (0.00) NA
Emergent CABG MI
5/111 (4.50)
3/55 (5.45)
0.803
TLR
3/111 (2.70)
1/55 (1.82)
0.690
TLR / TVR
6/111 (5.40)
0.269

50. Inspiron Registry Baseline Clinical Characteristics (n=371 pts)
Male
63.3
Age, years
62.9 ± 10.6
Diabetes
50.7
Insulin-requiring DM
14.6
Acute coronary syndrome
39.6
Multivessel disease
69.2
2-vessel CAD
35.8
3-vessel CAD
33.4
Heart failure
15.6
Previous coronary treatment
48.5
Previous PCI
Previous CABG
18.1
Numbers are average ± standard deviation or percentages
CABG = coronary artery bypass graft surgery; CAD = coronary artery disease; DM = diabetes mellitus; PCI = percutaneous coronary intervention

51. Inspiron Registry Clinical Outcomes (n=371 pts; K-M estimates)
Mean 1.6 stents/pt (34.3 mm length)
30 days
180 days
Overall death
0.8
1.6
Myocardial infarction
Peri-procedural
4.0 -
Non-peri-procedural
1.3
Target vessel revascularization
2.8
Any major cardiac adverse event
4.6
9.0
Stent thrombosis
0.5
Possible
Probable
Definite

52. Emerging DES with BP Abluminus (Envision Scientific, India)
Alex (Balton, Poland)
BioMime (Meril Life Sciences, India)
FireHawk (MicroPort, China)
Inspiron (Scitech, Brazil)
BuMA (SinoMed, China)

58. Conclusions
New emerging DES with biodegradable polymer technology incorporate advanced thin cobalt-chromium platforms, abluminal coating and relatively low drug dose (mainly sirolimus)
Overall, all systems have demonstrated high efficacy on inhibiting NIH and low event rates
Comparative, non-inferiority studies evaluating their performance and clinical impact in complex, real world scenarios comparison to current gold standard DES

59. Thanks!